4-trifluoromethylsalicylamides



United States Patent 2,967,194 '4-TRIFLUOROMETHYLSALICYLAM I DES MurrayHauptschein, Glenside, Pa., assignor to Pennsalt Chemicals Corporation,Philadelphia, Pa., a corporation of Pennsylvania No Drawing. Filed May15, 1958, Ser. No. 735,643

6 Claims. (Cl. 260-473) This invention relates to novel aminoderivatives of 4- trifiuoromethylsalicylic acid. Particularly it relatesto compounds represented by the formula CFs wherein R includes amino,phenylamino, hydrazino (aminoamiuo), and hydroxylamino. Moreparticularly it relates 'to 4-trifluoromethylsalicylamide (I),4-trifluoromethylsalicylanilide (II), 4-trifluoromethylsalicylic acidhydraxide (III), and 4-trifluoromethylsalicylhydroxamic acid (IV), asshown in Table I.

This application is a continuation-impart of Serial No. 447,390, filedAugust 2, 1954, now abandoned.

The amino derivatives of 4-trifiuoromethylsalicylic acid of thisinvention are useful as anti-mildew and anti-fungal agents. They arealso useful as chemical intermediates for the preparation of otherderivatives of 4-trifiuoromethylsalicylic acid wherein the amino groupis coupled to other molecular structures to form other fungicidalcompounds. The amino compounds are additionally useful as antioxidantsand corrosion inhibitors in lubricating oils.

The compounds of this invention are derived in general from4-trifluorornethylsalicylic acid which is disclosed and claimed in saidparent application. They are prepared by replacing the hydroxyl radicalof the carboxyl group of said 4-trifluoromethylsalicylic acid directlyor indirectly with an amino or substituted amino group derived fromknown reagents by procedures known in the art, as shown in the exampleswhich follow.

The following examples of the preparation of my novel compounds arepresented for the purpose of illustrating 2,967,194 Patented Jan. 3,1961 the invention, and it is to be understood that the inven-- tion isnot to be restricted to these examples.

A mixture of 10.3 g. of 4-trifluoromethylsalicylic acid, 5.12 g. ofaniline and 15 cc. of dimethylaniline was heated; at 100 C. until theacid dissolved, and 5 cc. of phosphorous trichloride were added dropwisewith stirring during ten minutes. The mixture was heated at 100-105" C.for an additional half-hour and then poured while hot into a wormsolution of 50 ml. concentrated hydrochloric acid and 200 ml. of waterwith vigorous stirring. The crude solid (10 g., 71% yield), was washedwith bicarbonate, dissolved in alkali and reprecipitated with acid.After several recrystallizations from 50% aqueous alcohol anddecolorization with charcoal, pure 4-fiuoromethylsalicyl anilide, M.P.189-190 C. (white powder), was obtained.

Analysis.-Calcd. for C H O NF C, 59.79; H, 3.58; N, 4.98. Found: C,59.69; H, 3.72; N, 4.94.

In preparing the amino, hydrazine, and hydroxylamino derivatives of4-trifluoromethylsalicylic acid, the 4-fluoromethylsalicylic acid isfirst converted to its methyl derivative as shown in Example 2 and thelatter methyl-4-trifluoromethylsalicylate is then converted to therespective amino derivatives as shown in Examples 3, 4, and 5.

Example 2.--Methyl 4-trifluor0methyIsalicylate Twenty and six-tenthsgrams of 4-trifiuoromethylsalicylic acid were esterified with 35 ml. ofmethanol in the presence of 3.5 ml. of concentrated sulfuric acid at thereflux temperature for 6 hours. Upon working up in the usual manner,there was isolated in yield (75% con-- Example3.4-triflu0r0methylsalicylamia'e Ten grams of methyl4-trifluoromethylsalicylate were. introduced slowly into a three-neckedflask containingg. of concentrated ammonia and 0.4 g. of powdered.aluminum and heated with stirring at 70 C. for two and one-quarterhours. Upon neutralization with a slight; excess of concentratedhydrochloric acid, 9 g. (97% yield) of crude4-trifluoromethylsalicylamide (M.P. 144 C.) were isolated. The solid waswashed with dilute sodium bicarbonate to remove possible traces oforganic acid. The precipitate was then redissolved upon acidification.Upon decolorization with charcoal and repeated crystallization fromaqueous alcohol, slightly pink needles of M.P. l49-15l C. were obtained.

Analysis.-Calcd. for C H O NF C, 46.84; H, 2.95;

Found: C, 47.04; H, 2.93; N, 6.58.

Example 4.4-triflu0r0methylsalicyIic acid hydrazide Eleven grams ofmethyl 4-trifluoromethylsalicylate were added dropwise to a refluxingsolution of 3 ml. of 85 hydrazine hydrate and 10 ml. absolute ethanol.After the addition of water, 10.5 g. of crude material were removed.This material consisted of the desired hydrazine and a product meltingat about 325 C. which is believed to be di(4-trifluoromethylsalicylicacid) hydrazine. After several recrystallizations from ethanol, 3.5 g.of white, crystalline 4-trifluoromethylsalicylic acid hydrazide, M.P.170.5l7l.5 C., were isolated.

Analysis.-Calcd. for C H O N F C, 43.64; H, 3.21; N, 12.73. Found: C,43.93;H, 3.36; N, 12.74.

Upon heating, the pure hydrazide melted to a clear colorless liquid at171 C. and upon continued heating formed a new solid at 180-181 C. withliberation of a gas. The new product melted at 319-321 C., with somedecomposition. It is believed that diacyl hydrazide formation tookplace.

Example 5 .4triflu0romethylsalicylhydroxamic acid Ten grams of methyl4-trifiuoromethylsalicylate were added with stirring to a mixture of6.95 g. of hydroxylamine hydrochloride, 11.8 g. of potassium hydroxide,160 ml. of water, and 100 ml. of ethanol. The reaction mixture wasallowed to stand at room temperature for one day. After addition ofhydrochloric acid and recrystallization from ethanol, 8.5 g. of palepink, almost white, 4- trifluorornethylsalicylhydroxamic acid, M.P.185.5186.0 C. were obtained.

Analysis.-Calcd.,for C H O NF C, 43.45; H, 2.74; N, 6.34. Found: C,43.74; H, 2.70; N, 6.45.

The amino 4-trifluoromethylsalicylates of this invention areparticularly useful as anti-mildew and fungicidal agents on cottonfabrics and cordage. In service the presence of the trifluoromethylradical on the aromatic ring of the salicylate enhances the potency ofthe compound over that of the comparable known amino salicylates.

The use of an amino 4-trifluoromethylsalicylate as an anti-mildew andfungicidal agent is demonstrated by the following example.

Example 6 Ten parts by weight of 4-trifluoromethylsalicylamide aredispersed in 100 parts of water made slightly alkaline with sodiumhydroxide. Cotton sheets are dipped into the solution, extracted anddried. The process is repeated if necessary until about 0.1% to about0.5% based on the Weight of the cloth of 4-trifiuoromethylsalicylamideis deposited thereon. The sheets are thereby rendered resistant togrowth of erysiphaceous fungi between laundering periods.

In a manner similar to that described in Example 6,4-trifluoromethylsalicylanilide, 4 trifluoromethylsalicylic acidhydrazide and 4-trifluoromethylhydroxyamic acid can be prepared and usedto mildewproof cotton and other cellulosic materials. All of my novelamino 4-trifluoromethylsalicylates may also be formulated intowaterbased wall paints where they will act as pesticidal agents.

Many different embodiments of this invention may be made withoutdeparting from the spirit and scope thereof, and it is to be understoodthat my invention includes also such embodiments and is not to belimited by the above description.

I claim:

1. Amino 4-trifluoromethylsalicylates represented by the formula CORwherein R is a member selected from the class consisting of amino,phenylamino, hydrazino, and hydroxylamino.

2. The compound 4-trifluoromethylsalicylamide.

3. The compound 4-trifluoromethylsalicylanilide.

4. The compound 4-trifiuoromethylsalicylic acid bydrazide.

5. The compound 4-trifiuoromethylsalicylhydroxamic acid.

6. The compound methyl 4-trifiuoromethylsalicylate.

References Cited in the file of this patent Hauptschein et al.: I. Am.Chem. Soc., 76, 1052, 4476-7, (1954).

UNITED STATES PATENT OFFICE CERTIFICATIGN OF CORRECTION Patent No.2,967,194

January 3, 1961 Murray Hauptschein It is hereby certified that errorappears in the above numbered patent requiring correction and that thesaid Letters Patent should read as corrected below.

Column 2', lines 16 and 17., for l fluoroiriethylsalicyl" read dtrifluoromethylsalicyl d fluoromethylsalicylic" read4-trifluoromethylsalicylic lines 22 and 23, for

(SEAL) Attest:

ERNEST W. SWIDER Attesting Officer DAVID L. LADD Commissioner of PatentsUNITED STATES PATENT OFT CERTIFICATION OF CORREC TION Patent No",2,367,194

January 3 1961 Murray Hauptschein It is hereby oer uified that error aent requiring correcti ppeai's in the above numbered paton and 'that thesa corrected below.

id Letters Patent should read as lines 16 and 17 for oromethylsalicyl"4-=fluoromethylsalicyl" alicylic lines 22 and 23, for readQ-trifluorome SEA L) Attest: Y

ERNEST W. SWIDER DAVID L. LADD Attesting Officer Commissioner of Patentsthylsalicylic UNITED STATES PATENT OFI E CERTIFICATION OF CORRECTIONPatent No 2,967,194 Janua ry 3I 1961 Murray Hauptsehe in I It is herebycertified that error app'eaifs in the above numbered patent requiringcorrection and that the said Letters Patent should read as correctedbelow.

Column 2 lines 16 and 17 for "4-fluoromethylsalicyl" read4=trifluor0methylsalicyl lines 22 and 23 for "4%luoromethylsalicylic"read 4-trifluoromethylsalicylic Signed and sealed this 23rd day of May1961 SEA L) Attest:

ERNEST W. SWIDER DAVID L. LADD Attesting Officer Commissioner of Patents

1. AMINO 4-TRIFLUOROMETHYLSALICYLATES REPRESENTED BY THE FORMULA
 6. THECOMPOUND METHYL 4-TRIFLUOROMETHYLSALICYLATE.